Microglial activation is a prominent feature throughout the optic pathway in experimental glaucoma. Pro-inflammatory microglial activation can contribute to neurodegeneration through the release of pro-inflammatory cytokines and other inflammatory mediators. Systemic administration of lipopolysaccharide (LPS), a constituent of gram-negative bacteria, stimulates microglia to produce pro-inflammatory cytokines and chemoattractants. A preliminary investigation demonstrated pro-inflammatory microglial activation throughout the optic pathway in rats following systemic LPS challenge (Fig.1). The aim of the current work was to investigate whether microglial priming with LPS would exacerbate optic nerve injury in rats following experimental glaucoma.

Methods

Adult female Sprague-Dawley rats were divided into LPS treatment (n = 15) and saline treatment groups (n = 15). Microglial priming was induced with a 2.5 mg/kg intraperitoneal injection of LPS; control animals received saline. Experimental glaucoma was induced 48 hours later in the right eyes of animals by laser photocoagulation of the trabecular meshwork. Animals were sacrificed nine days after laser treatment, and globes and optic nerves were harvested for histology and immunohistochemistry. Toluidine-blue stained sections were used to count optic nerve axons.

Results

The estimated number of axons per optic nerve was 51 327 ± 3868 (mean ± SEM) in the LPS group and 54 569 ± 6687 (mean ± SEM) in the saline group (Fig.2). Estimated optic nerve axon counts were not significantly different between groups (p = 0.67).

Conclusions

Systemic LPS challenge had no discernible effect on optic nerve injury in laser-induced experimental glaucoma. This finding does not support the hypothesis that this model of experimental glaucoma involves inflammation and instead suggests that microglial activation may occur secondary to chronic neurodegeneration.